A Randomized, Double-Blind, Placebo-Controlled Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Orally Administered VG290131 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- VG290131
- Conditions
- Healthy Volunteers
- Sponsor
- Zhejiang Vimgreen Pharmaceuticals, Ltd.
- Enrollment
- 86
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability of VG290131 by physical examinations
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled phase I study to evaluate the safety, tolerability and PK profiles of orally administered VG290131 in healthy subjects. The main questions it aims to answer are:
- The safety and tolerability of VG290131 when administered orally as a single dose and multiple doses in healthy subjects.
- The pharmacokinetic (PK) profiles of VG290131 and the food effect on the PK profiles of VG290131 in healthy subjects.
Approximately 86 subjects will be enrolled in the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject will be eligible for inclusion in this study only if all of the following criteria are met:
- •Willing to comply with protocol required visit schedule and visit requirements and provide written ICF;
- •Healthy adult male and female subjects, aged 18 to 45 years of age (inclusive) at the time of signing the ICF;
- •Body mass index between 18.0 and 32.0 kg/m2, inclusive;
- •Considered medically healthy as determined by the investigator, based on medical history and clinical evaluations including physical examination, clinical laboratory tests, vital sign measurements, and 12-Lead ECG;
- •Male subjects must agree to practice true abstinence; be surgically sterilized (performed at least 6 months prior to screening and documented to no longer produce sperm - verbal confirmation through medical history review acceptable); or agree to use a condom plus effective contraception methods for their female partner, if of childbearing potential, from the signing of ICF to 3 months after the last dose of IMPs and refrain from donating sperm during this period. These contraception requirements do not apply if the male subject is in an exclusively same sex relationship;
- •Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- •Women of non-childbearing potential (WONCBP), defined as surgically sterile (hysterectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral oophorectomy - verbal confirmation through medical history review acceptable) or postmenopausal (no menses for 12 months and confirmed by follicle stimulating hormone \[FSH\] level ≥40 mlU/mL);
- •WOCBP and agree to practice true abstinence or agrees to use a highly effective method of contraceptions consistently from the signing of ICF to 3 months after the last dose of investigational medicinal products \[IMPs\] and refrain from donating eggs during this period. And WOCBP must have a negative serum and/or urine pregnancy test result within 7 days prior to the first dose of IMPs.
- •Subject is in an exclusively same-sex relationship.
Exclusion Criteria
- •A subject meeting any of the following exclusion criteria will not be allowed to participate in this study:
- •Ascertained or presumptive hypersensitivity (including allergies) to any ingredient of the VG290131; history of other significant allergies or anaphylaxis, as determined by the investigator;
- •Considered by the investigator to be ineligible for the study due to a history of or current condition of significant metabolic or endocrine, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, immunological, neurological, or psychiatric disorders with clinical manifestations;
- •Active or history of serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression, which require current pharmacological intervention;
- •History of stomach or intestinal surgery or resection diseases including but not limited to, gastric band/gastric resection and/or intestinal resection and/or duodenal disease (i.e. celiac disease) which may potentially alter absorption and/or excretion of VG290131 (except for an appendectomy);
- •Used drugs or substances known to be inducers or inhibitors of cytochrome P450 enzymes or P-glycoprotein (P-gp) substrates within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMPs;
- •Used prescription or over-the-counter (OTC) drugs (with the exception of hormonal contraception, menopausal hormone replacement therapy or occasional analgesics such as Paracetamol \[1 g per dose and maximum 2-4 g per day\], Ibuprofen and standard daily vitamins etc. in short term at the Investigator's discretion), within 14 days or 5 half-lives (whichever is longer) prior to the first dose of IMPs;
- •Participated in any other investigational trials or has been exposed to other investigational drugs within 28 days or 5 half-lives of the previously administered investigational drug, whichever is longer, prior to the first dose of IMPs;
- •Smoking ≥ 5 cigarettes per day (or an equivalent amount of any other nicotine-containing products) within 6 months before screening or unable to stop smoking during the study;
- •Alcohol consumption of \> 21 units per week for males and \> 14 units per week for females within the 6 months before screening (1 unit=360 mL of beer or 45 mL of spirits with an alcohol content of ≥ 40% or 150 mL of wine) or a positive result of alcohol breath test on admission or unable to abstain from consuming alcohol from 24 h prior to admission, until completion of the end of study (EOS) visit;
Arms & Interventions
SAD Cohort 1
In SAD Cohort 1, 8 subjects will be randomized to receive a single dose of VG290131 (1 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).
Intervention: VG290131
SAD Cohort 2 (FE Study)
SAD Cohort 2 (FE study) is a two-sequence, two-period crossover study. A total of 14 healthy subjects will be randomized to two dosing sequences in a 1:1 ratio. Subjects in sequence 1 will receive a single dose of VG290131 (5 mg) or placebo under fasted condition in Period 1 and under fed condition in Period 2. Subjects in sequence 2 will be administered under fed condition in Period 1 and under fasted condition in Period 2. There will be a 7-day washout between the two dosing periods. Two sentinel subjects will be enrolled in the two dosing sequences of Period 1, respectively: one subject will be randomized to receive VG290131 (5 mg), and the other subject will be randomized to receive placebo. After the investigator reviews safety/tolerability information on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in that sequences will be randomized to receive VG290131 (n=4) and placebo (n=1). No sentinel subjects in Period 2.
Intervention: VG290131
SAD Cohort 3
In SAD Cohort 3, 8 subjects will be randomized to receive a single dose of VG290131 (25 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).
Intervention: VG290131
SAD Cohort 4
In SAD Cohort 4, 8 subjects will be randomized to receive a single dose of VG290131 (50 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).
Intervention: VG290131
SAD Cohort 5
In SAD Cohort 5, 8 subjects will be randomized to receive a single dose of VG290131 (100 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).
Intervention: VG290131
SAD Cohort 6
In SAD Cohort 6, 8 subjects will be randomized to receive a single dose of VG290131 (200 mg) (n=6) or matching placebo (n=2), respectively. To ensure the safety of the subjects, two sentinel subjects will be enrolled first: one subject will be randomized to receive VG290131, and the other subject will be randomized to receive a placebo. After the investigator reviews safety/tolerability information available on the sentinel subjects after 24 h and no significant safety issues are observed, the subsequent subjects in the cohort will be randomized to receive VG290131 (n=5) and placebo (n=1).
Intervention: VG290131
MAD Cohort 1
In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (1 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.
Intervention: VG290131
MAD Cohort 2
In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (5 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.
Intervention: VG290131
MAD Cohort 3
In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (25 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.
Intervention: VG290131
MAD Cohort 4
In MAD Cohort 1, 8 subjects will be randomized 3:1 to receive a once or twice daily dose of VG290131 (100 mg) (n=6) or matching placebo (n=2) for 7 consecutive days depending on the PK profiles of the SAD study, respectively.
Intervention: VG290131
Outcomes
Primary Outcomes
To evaluate the safety and tolerability of VG290131 by physical examinations
Time Frame: From admission to discharge, up to 12 days.
To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in physical examinations (Skin and mucosa, lymph nodes, head, eyes, ears, nose, and throat (HEENT), chest, abdomen, spine and limbs, musculoskeletal system, and nervous system).
To evaluate the safety and tolerability of VG290131 by vital signs
Time Frame: From admission to discharge, up to 12 days.
To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in vital signs (Blood pressure, heart rate, body temperature, and respiration rate).
To evaluate the safety and tolerability of VG290131 by clinical laboratory tests
Time Frame: From admission to discharge, up to 12 days.
To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in clinical laboratory tests (hematology, coagulation, biochemistry and urine analysis).
To evaluate the safety and tolerability of VG290131 by TEAEs
Time Frame: From admission to discharge, up to 12 days.
To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the incidence, severity, and causality of treatment-emergent adverse events (TEAEs).
To evaluate the safety and tolerability of VG290131 by 12-Lead ECG
Time Frame: From admission to discharge, up to 12 days.
To evaluate the safety and tolerability of VG290131 after SAD and MAD doses to healthy volunteers by assessing the number and percentage of subjects with clinically significant changes in 12-Lead ECG (RR, PR, QRSD, QT, and QTc).
Secondary Outcomes
- To evaluate PK parameter Tmax of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter Cmin,ss of VG290131 after multiple doses(From admission to discharge, up to 12 days.)
- To evaluate PK parameter AUC0-t of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter AUC0-inf of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter CL/F of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter λz of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter Cmax of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter t1/2 of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter Vz/F of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter Cmax,ss of VG290131 after multiple doses(From admission to discharge, up to 12 days.)
- To evaluate PK parameter MRT of VG290131 after a single dose(From admission to discharge, up to 12 days.)
- To evaluate PK parameter AUCss of VG290131 after multiple doses(From admission to discharge, up to 12 days.)
- To evaluate PK parameter Rac of VG290131 after multiple doses(From admission to discharge, up to 12 days.)
- To evaluate PK parameter Cav,ss of VG290131 after multiple doses(From admission to discharge, up to 12 days.)